It has been reported that uptake of soybean or processed soybean products alleviates the risk of carcinogenesis and participates in the prevention of primary or chemical induced cancers. This effect is attributable to isoflavones contained in soybean. Soybean isoflavones have estrogen-like effects and it has been demonstrated that they have a wide variety of physiological effect to prevent cancers such as breast cancer, colorectal cancer and prostatic cancer, cardiovascular diseases, brain dysfunction, osteoporosis, alcohol dependence, menopause, hyperlipemia and the like.
As the soybean isoflavones, genistin, daidzin, glycitin and the like are known. They are glucose glycosides having genistein, daidzein and glycitein, respectively, as an aglycone. The soybean isoflavones occur in soybean seeds in the form of glucose glycoside or derivatives thereof.
The physiological effect of soybean isoflavones is mainly based on the effect of their aglycone but not glycoside. This is because they are difficult to be absorbed through the small intestine as long as they remain in that form.
Several methods for decomposing the soybean isoflavone glycosides to give their aglycone have been proposed. For example, a method of converting soybean isoflavone glycosides to aglycones by the action of β-glucosidase in soybean (Japanese Patent Application Laid-open No. Hei 1-258669), a method of extracting isoflavone aglycone produced in soy sauce cake or soy sauce oil (Japanese Patent Application Laid-open No. Hei 5-170756), a method of allowing Aspergillus sp. to act on soybean protein to give an isoflavone compound containing the aglycone (Japanese Patent Application Laid-open No. Hei 8-214787), a method of extracting a plant protein and then converting it to aglycone by the action of β-glucosidase or esterase (Published Translation Japanese Patent Application No. Hei 9-503781 and U.S. Pat. No. 5,763,389), a method of allowing an enzyme originated from a microbe to act on the hypocotyl of soybean to convert an isoflavone compound contained therein to its aglycone (Japanese Patent Application Laid-open No. Hei 11-89589), and so on.
Among the aglycones, in particular genistein exhibits physiological activities of tyrosine kinase inhibition, DNA topoisomerase inhibition, angiogenesis suppression and the like. In this case, however, genistein must be present in high concentrations in plasma in order to obtain sufficient physiological activities such as angiogenesis suppression. It is difficult to supply a necessary amount of genistein only by the uptake of genistin, which is a glycoside and hardly absorbed through the enteron. Consequently, in order to obtain sufficient effects of physiologic activities, the necessary amount must be taken up in the form of genistein, which is an aglycone.
On the other hand, basidiomycetes, for example, the mycelia or cultures of Lentinus edodes or Ganoderma applanatum are known to exhibit physiological effects such as immune enhancement effect and anti-tumor effect, and some of the basidiomycetes are used as anticancer agent.
In recent years, these anti-cancer agents are used mostly in combination with substances that have tumor angiogenesis inhibition effects. This is because use of substances with different mechanisms of action in combination on the same target of treatment promises high therapeutic effects.
As the substances with tumor angiogenesis inhibition effects, for example, those prepared from shark cartilage, which is a mixture of mucopolysaccharides, as a raw material, angiostatin and the like are known and some of them are put into practical use.
The term “tumor angiogenesis inhibition effects” means the effect of suppressing or inhibiting the activity of a grown tumor that produces an anigogenesis promoter by itself to generate blood vessels in order to supply nutrients and oxygen necessary for its growth.
The tumor angiogenesis inhibitor is a substance that prevents the angiogenesis of tumor cells to thereby suppresses or inhibits its hypergenesis. It is useful in the therapy of cancers since administration of it can lead to eradication of tumors.
The tumor angiogenesis inhibitor is effective when it is taken orally or intravenously injected. Currently few can be administered orally. Intravenous injection is disadvantageous since it requires a great burden on the part of patients.
The shark cartilage used for oral uptake must be taken in a large amount, for example, about 20 g or more per day but it has disadvantages that it has a fishy smell and an objectionable taste and is hard to take. For imparting the properties of suppressing the undesirable smell and taste and having it reached to the intestine without being dissolved in the stomach, which is in a strongly acidic condition, and allowing it to be dissolved and absorbed in the intestine, there have been performed cumbersome treatments. For example, shark cartilage has been pulverized to form fine powder, and such a fine powder has been coated with oil or sugar and the like.
Moreover, angiostatin has not been put into practice yet. Accordingly, a tumor angiogenesis inhibitor that can be orally administered and is highly safe is keenly demanded.